Singlet oxygen scavenger

ABSTRACT

A singlet oxygen scavenger includes, as an active component, hexyl diethyl amino hydroxy benzoyl benzoate, 1-(4-methoxy phenyl)-3-(4-tert-butyl phenyl)-1, 3-propanedione, terephthalylidene-3,3′-dicamphor-10,10′-disulfonate, 2-ethyl hexyl 4-methoxy cinnamate, or 2-ethyl hexyl 2-cyano-3,3-diphenyl acrylate; or 2-phenyl benzimidazole-5-sulfonic acid, 4,4′,4″-[(1,3,5-triazine-2,4,6-triyl) tris (imino)]trisbenzoic acid tris (2-ethyl hexyl), octyl salicylate, or 3,3,5-trimethyl cyclohexyl salicylate; or 2-hydroxy-4-methoxy-5-(sodiooxysulfonyl) benzophenone, drometrizol trisiloxane, 2-hydroxy-4-methoxy benzophenone, or 4-methyl benzylidene camphor.

TECHNICAL FIELD

The present disclosure relates to a singlet oxygen scavenger.

BACKGROUND ART

Humans live by utilizing oxygen, but some oxygen is active oxygen, andthis active oxygen is known to cause various diseases and aging. Activeoxygen species generated by ultraviolet rays are also recognized ascausing skin damage and premature aging. Substances that exhibit theaction of eliminating the active oxygen species are also known. Forexample, benzophenone derivatives derived from Hypericaceae plants(Patent Document 1), flavonoids and tannins derived from plant extracts(patent document 2), various plant extracts, and2-hydroxy-4-methylbenzophenone-5-sulfate (Patent Document 3), and thelike are known as substances that have radical scavenging activity.

Incidentally, active oxygen species are roughly classified into radicaltypes and non radical types. Hydroxy radicals (.OH), alkoxy radicals(LO.), peroxy radicals (LOO.), hydroperoxy radicals (HOO.), nitric oxide(NO.), nitrogen dioxide (NO₂.), superoxide (O₂ ⁻. )etc. are radicaltypes of active oxygen, in descending order of reactivity. Non-radicalsinclude singlet oxygen (¹O₂), ozone (O₃), hydrogen peroxide (H₂O₂),lipid hydroperoxide (LOON), etc. That is, what have been conventionallyreferred to as active oxygen species include those which are radical andnon radical, and there are reducing molecular species in which thenumber of electrons is different from that of ground state oxygen, suchas superoxide, hydroxy radical, and hydrogenated hydrogen peroxide. Inaddition, there is singlet oxygen, which is an excited molecular speciesthat has the same number of electrons as the ground state oxygen but isin an excited state. These species have unique properties according to anarrow definition, based on the differences in the states of electronstherein.

Among active oxygen species, superoxide and hydroxy radicals, forexample, react with proteins and readily cause fragmentation, butsinglet oxygen forms crosslinks to proteins and polymerizes proteins,and exhibits a unique reactivity which is completely different from suchradical active oxygen species such as superoxide etc. In addition,because singlet oxygen has a denaturing action on protein, it has alsobecome clear that singlet oxygen causes peroxidation of sebum whichcauses various skin troubles. However, as described above, active oxygenspecies have unique characteristics depending on the types thereof. Forexample, it cannot be predicted whether a radical active oxygenscavenger such as that which is disclosed in Patent Document 3 willfunction as a singlet oxygen scavenger.

From these viewpoints, studies specializing in singlet oxygen scavengersin particular have also been conducted. For example, Patent Document 4discloses a colloid of platinum or rhodium that containspolyvinylpyrrolidone, Patent Document 5 discloses a rosemary extract,Patent Document 6 discloses a humus soil extract, and Patent Document 7discloses an aloe juice as a singlet oxygen scavenger, respectively.

BACKGROUND ART DOCUMENTS Patent Documents [Patent Document 1]

Japanese Unexamined Patent Publication No. H 10-121044

[Patent Document 2]

Japanese Unexamined Patent Publication No. 2003-26560

[Patent Document 3]

Japanese Unexamined Patent Publication No. 2001-122765

[Patent Document 4]

Japanese Patent No. 4763460

[Patent Document 5]

Japanese Patent No. 5770428

[Patent Document 6]

Japanese Patent No. 5883226

[Patent Document 7]

Japanese Unexamined Patent Publication No. 2013-173681

SUMMARY OF DISCLOSURE Technical Problem

However, substances which are known as singlet scavengers have poorchemical stability. Therefore, they deteriorate during storage overtime, and the singlet oxygen scavenging function of many of themdecrease. Accordingly, there is demand for improvements in thepersistence of singlet oxygen scavenging effect.

The present disclosure has been developed in view of the foregoingcircumstances. The present disclosure provides a singlet oxygenscavenger having a high signet oxygen scavenging function.

Solution to Problem

A first singlet oxygen scavenger of the present disclosure has benzyldiethyl amino hydroxy benzoyl benzoate, 1-(4-methoxyphenyl)-3-(4-tert-butyl phenyl)-1,3-propanedione,terephthalylidene-3,3′-dicamphor-10,10′-disulfonate, 2-ethyl hexyl4-methoxy cinnamate, or 2-ethyl hexyl 2-cyano-3,3-diphenyl acrylate asan active component.

A second singlet oxygen scavenger of the present disclosure has 2-phenylbenzimidazole-5-sulfonic acid, 4,4′,4″-[(1,3,5-triazine-2,4,6-triyl)tris (imino)] trisbenzoic acid tris (2-ethyl hexyl), octyl salicylate,or 3,3,5-trimethyl cyclohexyl salicylate as an active component.

A third singlet oxygen scavenger of the present disclosure has2-hydroxy-4-methoxy-5-(sodiooxysulfonyl) benzophenone, drometrizoltrisiloxane, 2-hydroxy-4-methoxy benzophenone, or 4-methyl benzylidenecamphor as an active component.

Advantageous Effects of Invention

The singlet oxygen scavenger of the present disclosure has a highsinglet oxygen scavenging function. Therefore, the singlet oxygenscavenger of the present disclosure may be utilized to suppress variousreactions that singlet oxygen is involved in.

DESCRIPTION OF EMBODIMENTS

The singlet oxygen scavenger of the present disclosure will be describedin detail below.

A first singlet oxygen scavenger of the present disclosure has benzyldiethyl amino hydroxy benzoyl benzoate, l-(4-methoxyphenyl)-3-(4-tert-butyl phenyl)-1,3-propanedione,terephthalylidene-3,3′-dicamphor-10,10′-disulfonate, 2-ethyl hexyl4-methoxy cinnamate, or 2-ethyl hexyl 2-cyano-3,3-diphenyl acrylate asan active component.

Benzyl diethyl amino hydroxy benzoyl benzoate is also referred to ashexyl diethyl amino hydroxy benzoyl benzoate, and the CAS Number thereofis 302776-68-7. Benzyl diethyl amino hydroxy benzoyl benzoate iscommercially available as Uvinul A Plus from BASF.

The CAS Number of 1-(4-methoxy phenyl)-3-(4-tert-butylphenyl)-1,3-propanedione is 70356-09-01, and 1-(4-methoxyphenyl)-3-(4-tert-butyl phenyl)-1,3-propanedione is commerciallyavailable as Parsol 1789 from DSM.

The CAS Number of terephthalylidene-3,3′-dicamphor-10,10′-disulfonate is92761-26-7, and terephthalylidene-3,3′-dicamphor-10,10′-disulfonate iscommercially available as Mexoryl SX from CHIMEX, and also as Ecamsulefrom SIGMA-ALDRICH.

The CAS Number of 2-ethyl hexyl 4-methoxy cinnamate is 5466-77-3, and2-ethyl hexyl 4-methoxy cinnamate is commercially available as ParsolMCX from DSM and as Uvinul MC80 from BASF.

The CAS Number of 2-ethyl hexyl 2-cyano-3,3-diphenyl acrylate is6197-30-4, and 2-ethyl hexyl 2-cyano-3,3-diphenyl acrylate iscommercially available as Parsol 340 from DSM, Uvinul N539T from BASF,and as Eusolex OCR from MERCK.

A second singlet oxygen scavenger of the present disclosure has 2-phenylbenzimidazole-5-sulfonic acid, 4,4′,4″-[(1,3,5-triazine-2,4,6-triyl)tris (imino)] trisbenzoic acid tris (2-ethyl hexyl), octyl salicylate,or 3,3,5-trimethyl cyclohexyl salicylate as an active component.

The CAS Number of 2-phenyl benzimidazole-5-sulfonic acid is 27503-81-7,and 2-phenyl benzimidazole-5-sulfonic acid is available as Eusolex 232from MERCK and as Parsol HS from DSM.

4,4′,4″-[(1,3,5-triazine-2,4,6-triyl) tris (imino)] trisbenzoic acidtris (2-ethyl hexyl) is also referred to as 2,4,6-tris [4-(2-ethyl hexyloxycarbonyl) anilino]-1,3,5-triazine), and the CAS Number thereof is88122-99-0. 4,4′,4″-[(1,3,5-triazine -2,4,6-triyl) tris (imino)]trisbenzoic acid tris (2-ethyl hexyl) is commercially available asUvinul T150 from BASF.

The CAS Number of octyl salicylate is 118-60-5, and octyl salicylate iscommercially available as Neoheliopan OS from SYMRISE. The CAS Number of3,3,5-trimethyl cyclohexyl salicylate is 118-56-9, and 3,3,5-trimethylcyclohexyl salicylate is commercially available as Neoheliopan HMS fromSYMRISE.

A third singlet oxygen scavenger of the present disclosure has2-hydroxy-4-methoxy-5-(sodiooxysulfonyl) benzophenone, drometrizoltrisiloxane, 2-hydroxy-4-methoxy benzophenone, or 4-methyl benzylidenecamphor as an active component.

The CAS Number of 2-hydroxy-4-methoxy-5-(sodiooxysulfonyl) benzophenoneis 6628-37-1, and 2-hydroxy-4-methoxy-5-(sodiooxysulfonyl) benzophenoneis commercially available as Uvinul MS40 from BASF.

The CAS Number of drometrizol trisiloxane is 155633-54-8, anddrometrizol trisiloxane is commercially available as drometrizoletrisiloxane from SIGMA-ALDRICH.

2-hydroxy-4-methoxy benzophenone is also referred to as benzophenone 3,and the CAS Number thereof is 131-57-7. 2-hydroxy-4-methoxy benzophenoneis commercially available from BASF.

The CAS Number of 4-methyl benzylidene camphor is 36861-47-9, and4-methyl benzylidene camphor is available as Parsol MBC from DSM.

It is possible to evaluate the singlet oxygen scavenging function of thesinglet oxygen scavenger of the present disclosure by a singlet oxygenquenching rate constant. In the Stern-Volmer equation below, kQ is asinglet oxygen quenching rate constant, [Q] is a concentration of thesinglet oxygen scavenger, τ₀ is the lifetime of singlet oxygen asolution to which the singlet oxygen scavenger is not added, and τ isthe lifetime of singlet oxygen a solution to which the singlet oxygenscavenger is added.

τ₀/τ=1+τ₀ ·kQ·[Q]

A line is obtained by plotting τ/τ₀ aginst [Q] (Stern-Volmer plot), andkQ can be derived from the slope of the line and the value of τ₀. Notethat in equations and experiments in which τ/τ₀ indicates an effect,τ₀/τ is utilized to obtain the rate constant.

The singlet oxygen scavenger of the present disclosure may be blendedwith pharmaceuticals, cosmetics (including medicinal cosmetics),supplements, foods and the like alone, or in combination with one ormore known additives according to conventional methods. Because singletoxygen is abundant on the skin surface, which is constantly in contactwith oxygen and exposed to ultraviolet rays, the singlet oxygenscavenger of the present disclosure is more useful in applications as anexternal preparation for skin. In addition, the reactions which aresuppressed by the elimination of singlet oxygen are reactions thatcontribute to skin aging, skin darkening, and skin damage, and thus thesinglet oxygen scavenger of the present disclosure which is capable ofsuppressing such reactions is particularly useful as a skin cosmetic forthe purpose of preventing skin aging, whitening and skin beautification.

The amount of the singlet oxygen scavenger of the present disclosure tobe blended differs depending on the singlet oxygen scavenger ability ofthe singlet oxygen scavenger in addition to the form of dosage, theintended purpose of use, etc. Generally, it is preferable for thecontent of the singlet oxygen scavenger to be within a range from 0.01to 20% by mass, and more preferably 0.1 to 10% by mass of an ultimatecomposition. Within this range, the singlet oxygen scavenger will becapable of being blended stably, and a superior singlet oxygenscavenging function will be capable of being exhibited.

The form of the singlet oxygen scavenger of the present disclosure maybe selected as appropriate according to the intended purpose, and thesinglet oxygen scavenger may be a liquid or a dried solid. The solid maybe a solid or a powder. In the case that the singlet oxygen scavenger isa solid, the solid may be dissolved or dispersed in a suitable liquid,or mixed with or adsorbed to a suitable powder carrier. In some cases,an emulsifying agent, a dispersing agent, a suspending agent, aspreading agent, a permeating agent, a moisturizing agent, a stabilizingagent, etc. may be added, and the singlet oxygen scavenger may beutilized in a preparation such as an emulsified agent, an oil basedagent, a wettable powder agent, a powder agent, a tablet, a capsule, anda liquid.

In the case that the singlet oxygen scavenger is utilized in an externalpreparation for the skin and a cosmetic, it may be in the form of aliquid, a gel, a cream, a semisolid, a solid, a stick, a powder, etc.The singlet oxygen scavenger may be utilized in an emulsion, a cream, alotion, a cosmetic liquid, a facial pack, a facial cleanser, a makeupcosmetic, a hair cosmetic, etc.

EXAMPLES

The singlet oxygen quenching function of the singlet oxygen scavenger ofthe present disclosure was evaluated by measuring a singlet oxygenquenching rate constant kQ by the following procedure.

<Measuring Devices> (1) Detector Near Infrared Photomultiplier TubeModule by HAMAMATSU PHOTONICS Model: H10330A-45, Wavelength Range: 950to 1400 nm (2) Spectrometer Miniature Spectrometer by SHIMADZU Model:SPG-1201R, Wavelength Range: 700 to 2500 nm (3) Light Source Nd:YAGLaser, Continuum (CONTINUUM, USA) Model: Surelite I, Wavelength Range:1064, 532, 355, and 266 nm (4) Data Processor Digital Oscilloscope,Tektronix (TEKTRONIX, USA) Model: TDS 3012C, Frequency Band: 100 MHz<Measurement Procedure> (Preparation of Samples)

Rose Bengal (RB), which is a red pigment, was dissolved in a solvent(selected as appropriate from among acetonitrile, acetone, and heavywater according to favorable solubility) as a photosensitizer forgenerating singlet oxygen. The concentration of RB was set such that theabsorbance at 532 nm was within an approximate range from 0.4 to 0.5.The RB solution was dissolved in a solvent so that each of the singletoxygen scavengers shown in Table 1 was of a predetermined concentration,and the solution was prepared and subjected to the followingmeasurement. In addition, the substances shown in Table 2 were preparedin a similar manner and subjected to the following measurement.

(Measurement)

RB was excited employing 532 nm light from the Nd: YAG laser (astructure in which yttrium, aluminum, and garnet single crystals aredoped with Nd⁺³ ions), and singlet oxygen was generated by energytransfer from RB to oxygen molecules. Only RB absorbs light at 532 nm,and the singlet oxygen scavengers do not. The light emitted from thesolutions that contain the singlet oxygen scavengers was dispersed bythe miniature spectrometer. 1274 nm near infrared phosphorescence, whichis specific to singlet oxygen, was detected with the near infraredphotomultiplier tube module and recorded on the digital oscilloscope.The attenuation curve of the near infrared phosphorescence emitted bythe singlet oxygen was analyzed, and the lifetime τ of singlet oxygen ateach concentration of the added singlet oxygen scavenger was obtained.In addition, the lifetime τ0 of singlet oxygen was determined in asolution to which no singlet oxygen scavenger was added (a solution withno added singlet oxygen scavenger).

The singlet oxygen quenching rate constant kQ was calculated by theaforementioned Stern-Volmer equation for each concentration [Q] of thesinglet oxygen scavenger, the lifetime τ0 without the addition of thesinglet oxygen scavenger, and the lifetime τ of singlet oxygen in thesolutions to which singlet oxygen scavengers were added. Table 1 showsthe results which were obtained.

The larger the singlet oxygen quenching rate constant kQ, the greaterthe singlet oxygen scavenging function.

TABLE 1 Singlet Oxygen Quenching Con- Rate cen- Constant kQ SubstanceName and CAS Number tration ✓τ_(o) (Solvent) 1 2-phenylbenzimidazole-5-sulfonic acid  3% τ/τ₀ = 1/28 3.5 × 10⁶ 2-phenylbenzimidazole-5-sulfonic acid (τ₀ = 64 μs) (D₂O NaOH) 27503-81-7 2 hexyldiethyl amino hydroxy benzoyl benzoate 10% τ/τ₀ = 1/60 3.5 × 10⁶ n-hexyl2-(4-diethylamino-2-hydroxybenzoyl)benzoate (τ₀ = 73 μs) (Acetonitrile)302776-68-7 3 2-hydroxy-4-methoxy-5-(sodiooxysulfonyl) benzophenone 10%τ/τ₀ = 1/5.1 2.0 × 10⁶ sodium 2-hydroxy-1-methoxybenzophenone-5sulfonate(τ₀ = 68 μs) (D₂O) 6628-37-1 4 Drometrizole trisiloxane 15% τ/τ₀ = 1/1.97.3 × 10⁴ 2-(2H-benzotriazol-2-yl)4-methyl-6-[2-methyl-3-[1,3,3,3- (τ₀ =54 μs) (Acetone) tetramethyl-1-[(trimethylsilyl)oxy]disiloxany]propyl]phenol 155633-54-8 5 1-(4-methoxy phenyl)-3-(4- 10% τ/τ₀ = 1/1.7 4.0 ×10⁴ tert-butyl-phenyl)-1.3-propanedione (τ₀ = 73 μs) (Acetonitrile)4-tert-butyl-4′-methoxydibenzoylmethane

 0356-09-1 6 terephthalylidene-3,3′-dicamphor-10,10′-disulfonate 10%τ/τ₀ = 1/1.4 3.6 × 10⁴terephthalylidene-3,3′-dicamphor-10,10′-disulfonate (τ₀ = 68 μs)(D₂O—KOH) 92761-26-7 7 2-ethyl hexyl 4-methoxy cinnamate 20% τ/τ₀ =1/1.6 1.4 × 10⁴ 2-ethylhexyl 4-methoxycinnamate (τ₀ = 73 μs)(Acetonitrile) 5466-77-3 8 2-ethyl hexyl 2-cyano-3,3-diphenyl acrylate10% τ/τ₀ = 1/1.2 1.2 × 10⁴ 2-ethylhexyl 2-cyano-3,3-diphenylacrylate (τ₀= 73 μs) (Acetonitrile) 6197-30-4 9 2-hydroxy-4-methoxy benzophenone  5%τ/τ₀ = 1/1.1 0.96 × 10⁴ 2-hydroxy-4-methoxybenzophenone (τ₀ = 73 μs)(Acetonitrile) 131-57-7 10 Octyl salicilate 10% τ/τ₀ = 1/1.2 8.0 × 10³2-ethylhexyl salicylate (τ₀ = 73 μs) (Acetonitrile) 118-60-5 11 4-methylbenzylidene camphor  4% τ/τ₀ = 1/1.04 4.3 × 10³4-methylbenzylidenecamphor (τ₀ = 73 μs) (Acetonitrile) 36861-47-9 12 3,3, 5-trimethyl cyclohexyl salicylate 10% τ/τ₀ = 1/1.20 9.2 × 10³3,3,5-trimethyl cyclohexyl salicylate (τ₀ = 73 μs) (Acetonitrile)118-56-9 13 4, 4′, 4″-[(1, 3, 5-triazine-2, 4,  5% τ/τ₀ = 1/1.09 3.5 ×10⁴ 6-triyl) tris (imino)] trisbenzoic acid tris (τ₀ = 54 μs) (Acetone)(2-ethyl hexyl) 2,4,6-tris[4-(2-ethylhexyloxycarbonyl)-anilino]-1,3,5-triazine 88122-99-0

indicates data missing or illegible when filed

As is clear from Table 1 and Table 2 below, it can be understood thatthe singlet oxygen scavenger of the present disclosure has a highsinglet oxygen scavenging function.

TABLE 2 Singlet Oxygen Con- Quenching Rate Substance Name cen- ConstantkQ and CAS Number tration ✓τ₀ (Solvent) 14 Bis(2-ethyl hexyl)- 10% τ/τ0= 1/1.02 Rate Constant naphthalene-2,6-dicarboxylate (τ0 = 14 μs notobtained diethylhexyl 2,6-napthalate ) Cmax = 0.2 mol 127474-91-3 dm⁻³(Acetone)

1-3. (Canceled)
 4. A method of scavenging singlet oxygen, by employingone of: hexyl diethyl amino hydroxy benzoyl benzoate; 1-(4-methoxyphenyl)-3-(4-tert-butyl phenyl)-1,3-propanedione;terephthalylidene-3,3′-dicamphor-10,10′-disulfonate; 2-ethyl hexyl4-methoxy cinnamate; and 2-ethyl hexyl 2-cyano-3,3-diphenyl acrylate. 5.A method of scavenging singlet oxygen, by employing one of: 2-phenylbenzimidazole-5-sulfonic acid; 4,4′,4″-[(1,3,5-triazine-2,4,6-triyl)tris (imino)] trisbenzoic acid tris (2-ethyl hexyl); octyl salicylate;and 3,3,5-trimethyl cyclohexyl salicylate.
 6. A method of scavengingsinglet oxygen, by employing one of:2-hydroxy-4-methoxy-5-(sodiooxysulfonyl) benzophenone; drometrizoltrisiloxane; 2-hydroxy-4-methoxy benzophenone; and 4-methyl benzylidenecamphor.